A Trial Comparing Unrelated Donor BMT With IST for Pediatric and Young Adult Patients With Severe Aplastic Anemia (TransIT, BMT CTN 2202)
TransIT
A Phase III Randomized Trial Comparing Unrelated Donor Bone Marrow Transplantation With Immune Suppressive Therapy for Newly Diagnosed Pediatric and Young Adult Patients With Severe Aplastic Anemia (TransIT, BMT CTN 2202)
3 other identifiers
interventional
53
2 countries
52
Brief Summary
Severe Aplastic Anemia (SAA) is a rare condition in which the body stops producing enough new blood cells. SAA can be cured with immune suppressive therapy or a bone marrow transplant. Regular treatment for patients with aplastic anemia who have a matched sibling (brother or sister), or family donor is a bone marrow transplant. Patients without a matched family donor normally are treated with immune suppressive therapy (IST). Match unrelated donor (URD) bone marrow transplant (BMT) is used as a secondary treatment in patients who did not get better with IST, had their disease come back, or a new worse disease replaced it (like leukemia). This trial will compare time from randomization to failure of treatment or death from any cause of IST versus URD BMT when used as initial therapy to treat SAA. The trial will also assess whether health-related quality of life and early markers of fertility differ between those randomized to URD BMT or IST, as well as assess the presence of marrow failure-related genes and presence of gene mutations associated with MDS or leukemia and the change in gene signatures after treatment in both study arms. This study treatment does not include any investigational drugs. The medicines and procedures in this study are standard for treatment of SAA.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_3
Started Jan 2023
Longer than P75 for phase_3
52 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 20, 2022
CompletedFirst Posted
Study publicly available on registry
October 31, 2022
CompletedStudy Start
First participant enrolled
January 25, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2029
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 1, 2029
February 17, 2026
October 1, 2025
6.9 years
October 20, 2022
February 12, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
The primary endpoint of this trial is time from randomization to treatment failure or death from any cause.
The median time to failure or death will be compared on the two arms using the log-rank test. Failure of IST is defined as the date that a second definitive therapy was recommended (BMT, second course of ATG) and failure of BMT defined as the date that a second definitive therapy was recommended (second BMT, course of ATG).
Randomization to 2 years post-randomization
Secondary Outcomes (27)
Comparison of subjects with failure of IST or BMT before or at 2 years
Randomization to 2 years post-randomization
Comparison of subjects with inadequate counts at 2 years among those who have not died or failed treatment.
Randomization to 2 years post-randomization
Comparison of subjects on immune suppression therapy at 2 years among those who have not died or failed treatment.
Randomization to 2 years post-randomization
Estimate the time from randomization to initiation of IST or BMT.
Randomization through Day 100
Comparison of the frequency of failure to receive primary assigned therapy (IST or BMT) and reasons for the failure.
Randomization through Day 100
- +22 more secondary outcomes
Study Arms (2)
Immunosuppressive Therapy
ACTIVE COMPARATORPatient will receive standard immunosuppressive therapy combination of drugs: horse anti-thymocyte globulin (ATG) and cyclosporine.
Matched Unrelated Stem Cell Transplant
ACTIVE COMPARATORPatient will under go matched unrelated donor transplant of hematopoietic stem cells as their therapy using fludarabine, cyclophosphamide, rabbit anti-thymocyte globulin (ATG), and low-dose total body irradiation (TBI) as preparative regimen and cyclosporine and methotrexate for graft versus host disease (GVHD) prevention.
Interventions
low-dose total body irradiation (TBI)
horse anti-thymocyte globulin (ATG)
rabbit anti-thymocyte globulin (ATG)
Matched Unrelated Donor (MUD) Hematopoietic Stem Cell Transplantation (HSCT)
Eligibility Criteria
You may qualify if:
- To be eligible to participate in the randomized trial, an individual must meet all the following criteria:
- Provision of signed and dated informed consent form for the randomized trial by patient and/or legal guardian.
- Age ≤25 years old at time of randomized trial consent.
- Confirmed diagnosis of idiopathic SAA, defined as:
- Bone marrow cellularity \<25%, or \<30% hematopoietic cells.
- Two of three of the following (in peripheral blood): neutrophils \<0.5 x 10\^9/L, platelets \<20 x 10\^9/L, absolute reticulocyte count \<60 x 10\^9/L or hemoglobin \<8 g/dL.
- No suitable fully matched related donor available (minimum 6/6 match for HLA-A and B at intermediate or high resolution and DRB1 at high resolution using DNA based typing).
- At least 2 unrelated donors noted on NMDP search who are well matched (9/10 or 10/10 for HLA-A, B, C, DRB1, and DQB1 using high resolution).
- In the treating physician's opinion, no obvious contraindications precluding them from BMT or IST.
You may not qualify if:
- Presence of Inherited bone marrow failure syndromes (IBMFS). The diagnosis of Fanconi anemia must be excluded by diepoxybutane (DEB) or equivalent testing on peripheral blood or marrow. Telomere length testing should be sent on all patients to exclude Dyskeratosis Congenita (DC), but if results are delayed or unavailable and there are no clinical manifestations of DC, patients may enroll. If patients have clinical characteristics suspicious for Shwachman-Diamond syndrome, this disorder should be excluded by pancreatic isoamylase testing or gene mutation analysis (note: pancreatic isoamylase testing is not useful in children \<3). Other testing per center may be performed to exclude IBMFS.
- Clonal cytogenetic abnormalities or Fluorescence In-Situ Hybridization (FISH) pattern consistent with pre- myelodysplastic syndrome (pre-MDS) or MDS on marrow examination.
- Known severe allergy to ATG.
- Prior allogeneic or autologous stem cell transplant.
- Prior solid organ transplant.
- Infection with human immunodeficiency virus (HIV).
- Active Hepatitis B or C. This only needs to be excluded in patients where there is clinical suspicion of hepatitis (e.g., elevated LFTs).
- Female patients who are pregnant or breast-feeding.
- Prior malignancies except resected basal cell carcinoma or treated cervical carcinoma in situ.
- Disease modifying treatment prior to study enrollment, including but not limited to use of androgens, eltrombopag, romiplostim, or immune suppression. Note: Supportive care measures such as G-CSF, blood transfusion support and antibiotics are allowable
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Pediatric Transplantation and Cellular Therapy Consortiumcollaborator
- Blood and Marrow Transplant Clinical Trials Networkcollaborator
- National Institutes of Health (NIH)collaborator
- National Heart, Lung, and Blood Institute (NHLBI)collaborator
- North American Pediatric Aplastic Anemia Consortiumcollaborator
- Boston Children's Hospitallead
- Center for International Blood and Marrow Transplant Researchcollaborator
Study Sites (52)
University of Alabama at Birmingham
Birmingham, Alabama, 35249, United States
Phoenix Children's Hospital
Phoenix, Arizona, 85016, United States
Arkansas
Little Rock, Arkansas, 72202, United States
Loma Linda
Loma Linda, California, 92354, United States
Children's Hospital Los Angeles
Los Angeles, California, 90027, United States
UCLA
Los Angeles, California, 90095, United States
Children's Hospital & Research Center Oakland
Oakland, California, 94609, United States
Children's Hospital of Orange County
Orange, California, 92868, United States
Stanford
Palo Alto, California, 94304, United States
Rady Children's Hospital San Diego
San Diego, California, 92123, United States
University of California San Francisco
San Francisco, California, 94158, United States
Children's Hospital Colorado
Aurora, Colorado, 80045, United States
Yale University
New Haven, Connecticut, 06520, United States
Nemours Children's Hospital, Delaware
Wilmington, Delaware, 19803, United States
Children's National Hospital
Washington D.C., District of Columbia, 20010, United States
University of Florida
Gainesville, Florida, 32610, United States
University of Miami
Miami, Florida, 33136, United States
Nicklaus Children's Hospital
Miami, Florida, 33155, United States
Johns Hopkins All Children's Hospital
St. Petersburg, Florida, 33701, United States
Children's Hospital of Atlanta/Emory
Atlanta, Georgia, 30322, United States
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, 60611, United States
University of Chicago
Chicago, Illinois, 60637, United States
Indiana University Hospital/Riley Hospital for Children
Indianapolis, Indiana, 46202, United States
Children's Hospital NOLA
New Orleans, Louisiana, 70118, United States
Maine Health
Scarborough, Maine, 04074, United States
Boston Children's Hospital
Boston, Massachusetts, 02115, United States
University of Michigan
Ann Arbor, Michigan, 48109, United States
Helen DeVos Children's Hospital
Grand Rapids, Michigan, 49503, United States
Mayo Clinic Rochestser
Rochester, Minnesota, 55902, United States
University of Mississippi Medical Center
Jackson, Mississippi, 39216, United States
Washington University in St. Louis
St Louis, Missouri, 63110, United States
Hackensack University Medical Center
Hackensack, New Jersey, 07601, United States
Roswell Park Comprehensive Cancer Center
Buffalo, New York, 14263, United States
Cohen Children's Medical Center of New York
New Hyde Park, New York, 11040, United States
Columbia University Medical Center
New York, New York, 10032, United States
University of North Carolina
Chapel Hill, North Carolina, 27599, United States
Levine Children's Hospital
Charlotte, North Carolina, 28203, United States
Duke University
Durham, North Carolina, 27705, United States
Nationwide Children's Hospital
Columbus, Ohio, 43205, United States
Oregon Health & Science University
Portland, Oregon, 97239, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104, United States
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105, United States
Vanderbilt University Medical Center
Nashville, Tennessee, 37203, United States
Children's Medical Center Dallas
Dallas, Texas, 75235, United States
Texas Children's Hospital
Houston, Texas, 77030, United States
Methodist Healthcare
San Antonio, Texas, 78229, United States
University of Utah/Primary Children's Hospital
Salt Lake City, Utah, 84112, United States
Children's Hospital of the King's Daughter
Norfolk, Virginia, 23507, United States
Fred Hutchinson Cancer Center
Seattle, Washington, 98109, United States
University of Wisconsin
Madison, Wisconsin, 53792, United States
British Columbia Children's
Vancouver, British Columbia, V6H 3V4, Canada
Winnipeg CancerCare Manitoba
Winnipeg, Manitoba, R3E 0V9, Canada
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
David Williams, MD
Boston Children's Hospital
- PRINCIPAL INVESTIGATOR
Michael Pulsipher, MD
University of Utah
- PRINCIPAL INVESTIGATOR
Bronwen Shaw, MD
CIBMTR/Medical College of Wisconsin (MCW)
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Chief - Division of Hematology/Oncology
Study Record Dates
First Submitted
October 20, 2022
First Posted
October 31, 2022
Study Start
January 25, 2023
Primary Completion (Estimated)
December 1, 2029
Study Completion (Estimated)
December 1, 2029
Last Updated
February 17, 2026
Record last verified: 2025-10